The Journal of Neuroscience, September 1, 2000, 20(17):6333-6339
Cbln3, a Novel Member of the Precerebellin Family that Binds
Specifically to Cbln1
Zhen
Pang,
Jian
Zuo, and
James I.
Morgan
Department of Developmental Neurobiology, St. Jude Children's
Research Hospital, Memphis, Tennessee 38105
Precerebellin (Cbln1) is the precursor of the brain-specific
hexadecapeptide cerebellin. Although cerebellin has properties of a
conventional neuropeptide, its function is controversial because Cbln1
has structural features characteristic of circulating atypical
collagens. Cbln1 is related to the three subunits of the complement C1q
complex. Therefore, we hypothesized that Cbln1 participated in
analogous heteromeric complexes with precerebellin-related proteins.
Using LexA-Cbln1 as bait in a yeast two-hybrid screen, we isolated a
cDNA encoding a novel Cbln1-related protein, designated Cbln3. The gene
encoding cbln3 had the same intron-exon structure as
cbln1 but mapped to a different mouse chromosome (14). The deduced amino acid sequence of Cbln3 was 55% identical to Cbln1 and
also contained a C1q signature domain and signal sequence for
secretion. In addition to binding avidly to Cbln3, Cbln1 also formed
homomeric complexes. In contrast, Cbln3 homomeric association was weak.
These interactions exhibited specificity because C1qB bound to neither
Cbln1 nor Cbln3. Like cbln1, cbln3 was expressed in the cerebellum and dorsal cochlear nucleus in which it was detected
in granule neurons. Because Cbln1 and Cbln3 are coexpressed in the
brain and interact avidly, they may function as a secreted heteromeric
complex in vivo.
Key words:
cerebellum; dorsal cochlear nucleus; granule cells; yeast
two-hybrid; C1q signature domain; gene mapping
Copyright © 2000 Society for Neuroscience 0270-6474/00/20176333-07$05.00/0